Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron
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Somatodendritic dopamine (DA) release from midbrain DA neurons activates D2 autoreceptors on these cells to regulate their activity. However, the source of autoregulatory DA remains controversial. Here, we test the hypothesis that D2 autoreceptors on a given DA neuron in the substantia nigra pars compacta (SNc) are activated primarily by DA released from that same cell, rather than from its neighbors. Voltage-clamp recording allows monitoring of evoked D2-receptor-mediated inhibitory currents (D2ICs) in SNc DA neurons as an index of DA release. Single-cell application of antibodies to Na + channels via the recording pipette decreases spontaneous activity of recorded neurons and attenuates evoked D2ICs; antibodies to SNAP-25, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, also decrease D2IC amplitude. Evoked D2ICs are nearly abolished by the light chain of botulinum neurotoxin A, which cleaves SNAP-25, whereas synaptically activated GABA B -receptor-mediated currents are unaffected. Thus, somatodendritic DA release in the SNc autoinhibits the neuron that releases it.
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The release of dopamine by SNc DA neurons can act on somatodendritic D2 receptors, thereby inhibiting dopamine release at DA axonal terminals in the striatum.
“previous studies have shown that the release of dopamine by SNc DA neurons can act on somatodendritic D2 receptors, thereby inhibiting dopamine release at DA axonal terminals in the striatum (Cragg and Greenfield 1997; Hikima et al. 2021; Sulzer et al. 2016).”
From Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism (2026) · cites this paper as Hikima et al. 2021
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Neuronal G protein-gated K<sup>+</sup> channels
Luo, H., Marron Fernandez de Velasco, E., & Wickman, K. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00102.2022 · Cited by 62 · see citing works
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- Authors
- Hikima, T., Lee, C. R., Witkovsky, P., Chesler, J., Ichtchenko, K., & Rice, M. E.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Corresponding author
- Rice, Margaret E.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 35
- Issue
- 1
- Pages
- 108951
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC8189326
- OpenAlex
- W3152378188
- Cited by
- 49
- References
- 4
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 3 · 2023: 7 · 2022: 14 · 2021: 2
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- substantia nigra pars compacta, autoinhibition, dopaminergic neurons, dopamine D1 receptor, dopamine D2 receptor
- MeSH terms
- Animals, Antibodies, Dendrites, Dopamine, Electric Stimulation, gamma-Aminobutyric Acid, Kinetics, Male, Mice, Inbred C57BL, Substantia Nigra, Receptors, Dopamine D2, Synaptosomal-Associated Protein 25, Mice, Inhibitory Postsynaptic Potentials, Single-Cell Analysis, Voltage-Gated Sodium Channels
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